We aimed to evaluate the major adverse cardiac events and other clinical outcomes in ST-segment-elevation myocardial infarction (STEMI) cases treated with prasugrel versus ticagrelor after percutaneous intervention (PCI). The study was a prospective comparative study into which 560 patients diagnosed with STEMI, being suitable for PCI, and prescribed with either prasugrel (n = 232) or ticagrelor (n = 328) as oral antiplatelet therapy were included. Patients were followed up for a mean of 10.9 ± 4.7 months and 11.9 ± 4.9 months for prasugrel and ticagrelor groups, respectively. The major adverse cardiac events developed in similar rates between prasugrel and ticagrelor groups (7.3% versus 7.9%, respectively, p = 0.793). Even if mortality rate was higher in ticagrelor group, the difference did not reach statistically significance (3.4% vs. 6.7%, p=0.092). Among all study population, stent thrombosis and minor bleeding was recorded only in 7 (1.2%) and 12 (2.1%) patients without significant difference between prasugrel and ticagrelor groups. Twenty patients (8.6%) in prasugrel group and 47 patients (14.3%) in ticagrelor group discontinued treatment (p = 0.023). In ticagrelor group, 12 patients discontinued treatment due to dyspnea, but none in prasugrel group (p = 0.001). Prasugrel and ticagrelor have similar effects on major adverse cardiac events in patients with STEMI undergoing primary PCI, but prasugrel seems more tolerated and less discontinued than ticagrelor.